Erythropoietin-producing hepatocellular carcinoma (Eph) receptors are highly conserved transmembrane proteins composed of multiple domains that participate in an array of complex cell signaling pathways. Vertebrates have sixteen Eph receptors, divided into two major classes, EphA (EphA1-EphA10) and EphB (EphB1-EphB6) based on sequence similarity in the extracellular domain and binding characteristics.
The Eph receptors interact with cell surface ligands called Eph receptor interacting proteins (ephrins). Currently, nine ephrins are known and are divided into two major classes (ephrin A1-6 and ephrin B1-3). Following binding of the Eph receptors and the ephrin ligands, which requires cell-cell interactions, propagation of signaling occurs bi-directionally into both the Eph receptor and the ephrin presenting cells. The signaling events resulting from these interactions are important in both neural development and during adulthood. For example, the Eph receptors together with ephrins participate in axon guidance by providing repulsive cues during axonal neurogenesis.
The EphB3 receptor subtype is expressed during embryonic development and in discrete areas of the adult brain, including the cerebellum and hippocampus. It co-localizes to brain regions with high levels of ephrin B ligand expression. EphB3 receptor expression also increases following central nervous system injury.